Genetic clonal diversity predicts progression to esophageal adenocarcinoma

Carlo C. Maley, Patricia C. Galipeau, Jennifer C. Finley, V. Jon Wongsurawat, Xiaohong Li, Carissa A. Sanchez, Thomas G. Paulson, Patricia L. Blount, Rosa Ana Risques, Peter S. Rabinovitch, Brian J. Reid

Research output: Contribution to journalArticle

488 Scopus citations

Abstract

Neoplasms are thought to progress to cancer through genetic instability generating cellular diversity1,2 and clonal expansions driven by selection for mutations in cancer genes3,4. Despite advances in the study of molecular biology of cancer genes5, relatively little is known about evolutionary mechanisms that drive neoplastic progression. It is unknown, for example, which may be more predictive of future progression of a neoplasm: genetic homogenization of the neoplasm, possibly caused by a clonal expansion, or the accumulation of clonal diversity. Here, in a prospective study, we show that clonal diversity measures adapted from ecology and evolution can predict progression to adenocarcinoma in the premalignant condition known as Barrett's esophagus, even when controlling for established genetic risk factors, including lesions in TP53 (p53; ref. 6) and ploidy abnormalities 7. Progression to cancer through accumulation of clonal diversity, on which natural selection acts, may be a fundamental principle of neoplasia with important clinical implications.

Original languageEnglish (US)
Pages (from-to)468-473
Number of pages6
JournalNature Genetics
Volume38
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Maley, C. C., Galipeau, P. C., Finley, J. C., Wongsurawat, V. J., Li, X., Sanchez, C. A., Paulson, T. G., Blount, P. L., Risques, R. A., Rabinovitch, P. S., & Reid, B. J. (2006). Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nature Genetics, 38(4), 468-473. https://doi.org/10.1038/ng1768